The long-range goal is to understand the mechanism of assembly, entry, and uncoating of viruses, by examining their structures in detail and by testing proposed mechanisms in biochemical experiments and by site-directed mutagenesis. (1) We will determine the structure of SV40, a simple dsDNA tumor virus, by X- ray crystallography, to a resolution of at 3.5 angstroms, and we will construct a molecular model. We will also use electron microscopy or x-ray diffraction, as appropriate, to examine other forms of the virion -- empty capsids and disassembly intermediates in order to gain insight into uncoating mechanisms. (2) We will determine the structure of murine polyomavirus to the limit of recordable diffraction (presently about 6 angstroms, and using this map and the SV4O structure we will build an approximate molecular model. (3) We will use the models of both viruses to develop specific proposals concerning the role in assembly of S-S bonds, Ca++ ions and covalent modification. We will test proposals where possible by constructing site-directed mutants (in collaboration with Prof. T. Benjamin). (4) We will use difference maps to look directly for sialic-acid binding sites since poloma requires sialic acid for initial binding to cells. (5) We will determine the structure of single-shelled rotavirus SA-11 particles by X-ray crystallography. Crystals are at hand that diffract to at least 8 angstroms, and we will use these crystals to study binding of peptides from the RER "receptor" of the single-shelled particles.